Once-Weekly Exenatide vs. Sitagliptin or Pioglitazone for Type 2 Diabetes

In patients with type 2 diabetes, incretin mimetic drugs stimulate glucose-related insulin secretion, attenuate glucagon release, and delay gastric emptying. Glucagon-like peptide-1 (GLP-1) receptor agonists such as the currently available formulation of exenatide (Byetta) require once- or twice-daily injections; a once-weekly subcutaneous formulation of exenatide is under FDA review. The oral dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin (Januvia) slows the degradation of endogenous GLP-1. Incretin mimetics are alternatives to sulfonylureas or thiazolidinediones when diabetes is not controlled by metformin alone.

With support from the developers of once-weekly exenatide, researchers randomized 491 adults with type 2 diabetes (glycosylated hemoglobin [HbA_1c] level, 7.1%–11.0% with stable metformin dosing) to add either exenatide (2 mg weekly) or maximal once-daily oral doses of sitagliptin (100 mg) or pioglitazone (Actos; 45 mg). Each patient also received oral or injected placebo.

After 26 weeks, exenatide lowered the mean HbA_1c level significantly more than either sitagliptin or pioglitazone (–1.5% vs. –0.9% and –1.2%). Patients who received exenatide also lost significantly more weight than those who took the other two agents (–2.3 kg vs. –0.8 kg and +2.8 kg). No major hypoglycemic episodes were reported. Nausea and diarrhea were the most common adverse events associated with exenatide and sitagliptin; upper respiratory infection and peripheral edema were the most common adverse events with pioglitazone.